The proposed investigation will extablish the responses of the intestinal, hepatic and splenic vascular beds to changes in plasma osmolarity. Blood flows and perfusion pressures will be recorded and hypertonic solutions infused into the superior mesenteric, inferior mesenteric, splenic and hepatic arteries. The resulting changes in regional vascular resistance will be calculated. In separate experiments, both the hepatic artery and the portal vein will be perfused in situ and hypertonic solutions infused into the hepatic portal vein. This preparation permits continous simultaneous assessment of changes in the hepatic arterial, portal venous and superior mesenteric vascular beds. Glucagon causes vasodilation in the small intestinal and hepatic arterial vascular beds. In addition, it antagonizes vasoconstrictor responses to sympathetic nerve stimulation or injected norepinephrine in these vascular beds. In this latter action, glucagon is unique amongst the peptide hormones of gastrointestinal and pancreatic origin. These observations will be extended to include 'physiological' concentrations of glucagon in the intestinal vasculature, and to study the colonic and splenic vascular beds. Glucagon may elicit both vasodilation and inhibition of vasoconstriction by an interaction with specific glucagon receptors, but in addition, it increases blood glucose and plasma osmolarity, and either or both of these effects may contribute to the hormone's vasoactivity. This investigation will elucidate the mechanism of action of glucagon on the splanchnic vascular bed.